Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exploration of antigenic determinants in spike glycoprotein of SARS-CoV2 and identification of five salient potential epitopes.

ABSTRACT: Emerging pathogens have been an eternal threat to mankind. In a series of pandemics caused by notorious coronaviruses, a newly emerged SARS-CoV2 virus is creating panic among the world population. The unavailability of reliable theranostics insists the exploration of antigenic determinants in spike glycoprotein of SARS-CoV2. The four novel inserts ('⁷⁰VSGTNGT⁷⁶', '¹⁵⁰KSWM¹⁵³', ²⁴⁷SYLTPG²⁵² and ⁶⁷⁴QTQTNSPRR⁶⁸²) in SARS-CoV2 spike protein were unraveled via multiple sequence alignment of spike proteins of SARS-CoV2, SARS-CoV, and MERS-CoV. The three-dimension (3D) modeling of the spike protein of the SARS-CoV2 and their interaction with the ACE2 receptor was delineated with the help of SWISS-MODEL and 3DLigandSite web servers. The predicted 3D model of SARS-CoV2 was further verified by SAVES, RAMPAGE, and ProSA-web tools. The potential B-cell immunogenic epitopes of SARS-CoV2 were predicted out by using various software viz. IEDB B-cell epitopes prediction tool, BepiPred linear epitope prediction tool, Emini Surface Accessibility Prediction tool, and Kolaskar-Tongaonkar antigenicity web tool. The five epitopes (i.e. '⁷¹SGTNGTKRFDN⁸¹, ²⁴⁷SYLTPG²⁵², ⁶³⁴RVYST⁶³⁸, ⁶⁷⁵QTQTNSPRRARSV⁶⁸⁷, and ¹⁰⁵⁴QSAPH¹⁰⁵⁸) were selected as potent antigenic determinants. The quantum of information generated by this study will prove beneficial for the development of effective therapeutics, diagnostics, and multi-epitopic vaccines to combat this ongoing menace.

SUBMITTER: Agrawal A

PROVIDER: S-EPMC8422955 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Generation of SARS-CoV-2 S1 Spike Glycoprotein Putative Antigenic Epitopes in Vitro by Intracellular Aminopeptidases.

Project description:Presentation of antigenic peptides by MHCI is central to cellular immune responses against viral pathogens. While adaptive immune responses versus SARS-CoV-2 can be of critical importance to both recovery and vaccine efficacy, how protein antigens from this pathogen are processed to generate antigenic peptides is largely unknown. Here, we analyzed the proteolytic processing of overlapping precursor peptides spanning the entire sequence of the S1 spike glycoprotein of SARS-CoV-2, by three key enzymes that generate antigenic peptides, aminopeptidases ERAP1, ERAP2, and IRAP. All enzymes generated shorter peptides with sequences suitable for binding onto HLA alleles, but with distinct specificity fingerprints. ERAP1 was the most efficient in generating peptides 8-11 residues long, the optimal length for HLA binding, while IRAP was the least efficient. The combination of ERAP1 with ERAP2 greatly limited the variability of peptide sequences produced. Less than 7% of computationally predicted epitopes were found to be produced experimentally, suggesting that aminopeptidase processing may constitute a significant filter to epitope presentation. These experimentally generated putative epitopes could be prioritized for SARS-CoV-2 immunogenicity studies and vaccine design. We furthermore propose that this in vitro trimming approach could constitute a general filtering method to enhance the prediction robustness for viral antigenic epitopes.

| S-EPMC7640968 | biostudies-literature

Identification of two antigenic epitopes on SARS-CoV spike protein.

Project description:The spike (S) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) is a major virion structural protein. It plays an important role in interaction with receptor and inducing neutralizing antibodies. In the study, six tentative antigenic epitopes (S1 S2 S3 S4 S5 S6) of the spike protein of SARS-CoV were predicted by bio-informatics analysis, and a multi-epitope chimeric gene of S1-S2-S3-S4-S5-S6 was synthesized and fused to downstream GST gene in pGEX-6p-1. The Western blotting demonstrated that SARS patient convalescent serum could recognize the recombinant fusion protein. A number of monoclonal antibodies were developed against the fusion protein. In further, the six predicted epitope genes were individually fused to GST of pGEX-6p-1 and expressed in Escherichia coli BL21, respectively. Among six fusion peptides, S5 reacted with monoclonal antibody D3C5 and S2 reacted with monoclonal antibody D3D1 against spike protein of SARS-CoV. The epitopes recognized by monoclonal antibodies D3C5 and D3D1 are linear, and correspond to 447-458 and 789-799 amino acids of spike protein of SARS-CoV, respectively. Identification of antigenic epitope of spike protein of SARS-CoV could provide the basis for the development of immunity-based prophylactic, therapeutic, and diagnostic techniques for the control of severe acute respiratory syndrome.

| S-EPMC7111154 | biostudies-literature

Generation of SARS-CoV-2 S1 spike glycoprotein putative antigenic epitopes in vitro by intracellular aminopeptidases

Project description:Presentation of antigenic peptides by MHCI is central to cellular immune responses against viral pathogens. While adaptive immune responses versus SARS-CoV-2 can be of critical importance to both recovery and vaccine efficacy, how protein antigens from this pathogen are processed inside the cell to generate antigenic peptides is largely unknown. Here, we analyzed the proteolytic processing of 315 overlapping precursor peptides spanning the entire sequence of the S1 spike glycoprotein of SARS-CoV-2, by three key enzymes for the generation ofthat generate antigenic peptides, namely intracellular aminopeptidases ERAP1, ERAP2 and IRAP. Each All enzymes generated shorter peptides with sequences suitable for binding onto HLA alleles, but with marked differences corresponding to distinct specificity fingerprints. ERAP1 was the most efficient in generating peptides 8-11 residues long, the optimal length for HLA binding, while IRAP was the least efficient. The combination of ERAP1 with ERAP2 was largely highly destructive and greatly reduced limited peptides the variability of peptide sequences availableproduced for HLA-binding. Less than 710% of computationally predicted epitopes were found to be produced by enzymatic trimming experimentally, suggesting that proteolytic aminopeptidase processing may constitute a significant filter to successful epitope presentation. These experimentally generated putative epitopes could be prioritized for SARS-CoV-2 immunogenicity studies and vaccine design. We furthermore propose that this in vitro trimming approach could constitute a general filtering method to enhance the prediction robustness of predicting for viral antigenic epitopes.

2021-11-25 | PXD019901 | Pride

In silico Design and Characterization of Multi-epitopes Vaccine for SARS-CoV2 from Its Spike Protein.

Project description:COVID 19 is a disease caused by a novel coronavirus, SARS-CoV2 originated in China most probably of Bat origin. Multiepitopes vaccine would be useful in eliminating SARS-CoV2 infections as asymptomatic patients are in large numbers. In response to this, we utilized bioinformatic tools to develop an efficient vaccine candidate against SARS-CoV2. The designed vaccine has effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes found antigenic, non-toxic and probably non-allergen. Modeled and the refined tertiary structure predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. The designed multiepitope vaccine has induced cell-mediated and humoral immunity along with increased interferon-gamma response. Macrophages and dendritic cells were also found to increase upon the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that the vaccine can be efficiently expressed in E. coli. In conclusion, the predicted vaccine is a good antigen, probable no allergen, and has the potential to induce cellular and humoral immunity.

| S-EPMC8722413 | biostudies-literature

Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine.

Project description:The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a major antigen for vaccine design. We previously demonstrated that the receptor-binding domain (RBD: residues 318-510) of S protein contains multiple conformation-dependent neutralizing epitopes (Conf I to VI) and serves as a major target of SARS-CoV neutralization. Here, we further characterized the antigenic structure in the RBD by a panel of novel mAbs isolated from the mice immunized with an inactivated SARS-CoV vaccine. Ten of the RBD-specific mAbs were mapped to four distinct groups of conformational epitopes (designated Group A to D), and all of which had potent neutralizing activity against S protein-pseudotyped SARS viruses. Group A, B, C mAbs target the epitopes that may overlap with the previously characterized Conf I, III, and VI respectively, but they display different capacity to block the receptor binding. Group D mAb (S25) was directed against a unique epitope by its competitive binding. Two anti-RBD mAbs recognizing the linear epitopes (Group E) were mapped to the RBD residues 335-352 and 442-458, respectively, and none of them inhibited the receptor binding and virus entry. Surprisingly, most neutralizing epitopes (Groups A to C) could be completely disrupted by single amino acid substitutions (e.g., D429A, R441A or D454A) or by deletions of several amino acids at the N-terminal or C-terminal region of the RBD; however, the Group D epitope was not sensitive to the mutations, highlighting its importance for vaccine development. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV, and this panel of novel mAbs can be used as tools for studying the structure of S protein and for guiding SARS vaccine design.

| S-EPMC7115380 | biostudies-literature

Bioinformatics prediction of B and T cell epitopes within the spike and nucleocapsid proteins of SARS-CoV2.

Project description:BackgroundThe striking difference in severity of SARS CoV2 infection among global population is partly attributed to viral factors. With the spike (S) and nucleocapsid (N) are the most immunogenic subunits, genetic diversity and antigenicity of S and N are key players in virulence and in vaccine development.AimThis paper aims at identifying immunogenic targets for better vaccine development and/or immunotherapy of COVID 19 pandemic.Methods18 complete genomes of SARS CoV2 (n=14), SARS CoV (n=2) and MERS CoV (n=2) were examined. Bioinformatics of viral genetics and protein folding allowed functional tuning of NH2 Terminal Domain (NTD) of S protein and development of epitope maps for B and T cell responses.ConclusionA deletion of amino acid residues Y144 and G107 were discovered in NTD of S protein derived from Indian and French isolates resulting in altered pocket structure exclusively located in NTD and reduced affinity of NTD binding to endogenous nAbs and disrupted NTD mediated cell entry. We therefore, proposed a set of B and T cell epitopes based on Immune Epitope Database, homologous epitopes for nAbs in convalescent plasma post SARS CoV infection and functional domains of S (NTD, Receptor Binding domain and the unique polybasic Furin cleavage site at S1/S2 junction). Nevertheless, laboratory data are required to develop vaccine and immunotherapeutics.

| S-EPMC7737509 | biostudies-literature

Novel antibody epitopes dominate the antigenicity of spike glycoprotein in SARS-CoV-2 compared to SARS-CoV.

Project description: Not available

| S-EPMC7091851 | biostudies-literature

Identification of destabilizing SNPs in SARS-CoV2-ACE2 protein and spike glycoprotein: implications for virus entry mechanisms.

Project description:COVID-19 an outbreak of a novel corona virus originating from Wuhan, China in December 2019 has now spread across the entire world and has been declared a pandemic by WHO. Angiotensin converting enzyme 2 (ACE2) is a receptor protein that interacts with the spike glycoprotein of the host to facilitate the entry of coronavirus (SARS-CoV-2) hence causing the disease (COVID-19). Our experimental design is based on bioinformatics approach that combines sequence, structure and consensus based tools to label a protein coding single nucleotide polymorphism (SNP) as damaging/deleterious or neutral. The interaction of wildtype ACE2-spike glycoprotein and their variants were analyzed using docking studies. The mutations W461R, G405E and F588S in ACE2 receptor protein and population specific mutations P391S, C12S and G1223A in the spike glycoprotein were predicted as highly destabilizing to the structure of the bound complex. So far, no extensive in silico study has been reported that identifies the effect of SNPs on Spike glycoprotein-ACE2 interaction exploring both sequence and structural features. To this end, this study conducted an in-depth analysis that facilitates in identifying the mutations that blocks the interaction of two proteins that can result in stopping the virus from entering the host cell.Communicated by Ramaswamy H. Sarma.

| S-EPMC7544926 | biostudies-literature

Immunoinformatics study to search epitopes of spike glycoprotein from SARS-CoV-2 as potential vaccine.

Project description:The Coronavirus disease named COVID-19 is caused by the virus reported in 2019 first identified in China. The cases of this disease have increased and as of June 1st, 2020 there are more than 216 countries affected. Pharmacological treatments have been proposed based on the resemblance of the HIV virus. With regard to prevention there is no vaccine, thus, we proposed to explore the spike protein due to its presence on the viral surface, and it also contains the putative viral entry receptor as well as the fusion peptide (important in the genome release). In this work we have employed In Silico techniques such as immunoinformatics tools which permit the identification of potential immunogenic regions on the viral surface (spike glycoprotein). From these analyses, we identified four epitopes E332-370, E627-651, E440-464 and E694-715 that accomplish essential features such as promiscuity, conservation grade, exposure and universality, and they also form stable complexes with MHCII molecule. We suggest that these epitopes could generate a specific immune response, and thus, they could be used for future applications such as the design of new epitope vaccines against the SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

| S-EPMC7332869 | biostudies-literature

Allotypic variation in antigen processing controls antigenic peptide generation from SARS-CoV-2 S1 spike glycoprotein.

Project description:Population genetic variability in immune system genes can often underlie variability in immune responses to pathogens. Cytotoxic T-lymphocytes are emerging as critical determinants of both severe acute respiratory syndrome coronavirus 2 infection severity and long-term immunity, after either recovery or vaccination. A hallmark of coronavirus disease 2019 is its highly variable severity and breadth of immune responses between individuals. To address the underlying mechanisms behind this phenomenon, we analyzed the proteolytic processing of S1 spike glycoprotein precursor antigenic peptides across ten common allotypes of endoplasmic reticulum aminopeptidase 1 (ERAP1), a polymorphic intracellular enzyme that can regulate cytotoxic T-lymphocyte responses by generating or destroying antigenic peptides. We utilized a systematic proteomic approach that allows the concurrent analysis of hundreds of trimming reactions in parallel, thus better emulating antigen processing in the cell. While all ERAP1 allotypes were capable of producing optimal ligands for major histocompatibility complex class I molecules, including known severe acute respiratory syndrome coronavirus 2 epitopes, they presented significant differences in peptide sequences produced, suggesting allotype-dependent sequence biases. Allotype 10, previously suggested to be enzymatically deficient, was rather found to be functionally distinct from other allotypes. Our findings suggest that common ERAP1 allotypes can be a major source of heterogeneity in antigen processing and through this mechanism contribute to variable immune responses in coronavirus disease 2019.

| S-EPMC8530767 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data